FGFRL1 deficiency reduces motility and tumorigenic potential of cells derived from oesophageal squamous cell carcinomas.

Abstract

Oesophageal squamous cell carcinoma (ESCC) is an aggressive cancer that resulted in ~400,000 mortalities worldwide in 2012. It was reported previously that fibroblast growth factor receptor-like 1 (FGFRL1) is highly expressed in ESCC patients with lymph node metastasis and poor prognosis accordingly. FGFRL1 is an FGFR that lacks tyrosine kinase activity, whereas the activity is critical for other FGFRs to activate intracellular signalling. The mechanism by which FGFRL1 promotes the aggressiveness of ESCCs is unknown. In the present study, two independent FGFRL1-deficient cell lines were generated from human ESCC KYSE520 cells, in order to investigate the relationship of FGFRL1 with the aggressiveness of ESCCs. FGFRL1-deficiency did not affect proliferation of KYSE520 cells in vitro. However, a xenograft mouse model demonstrated that FGFRL1-deficiency decelerated tumour growth in vivo. The haematoxylin-eosin staining identified that FGFRL1-deficient cells formed well-differentiated squamous cell carcinomas, whereas wild-type cells formed moderately differentiated squamous cell carcinomas. Microarray analysis of mRNA expression revealed that FGFRL1-depletion resulted in decreased expression of proteins associated with motility and invasion of tumour cells, matrix metalloproteinase-1 and fibroblast growth factor binding protein 1. The wound-healing assay indicated that depleting FGFRL1 reduced cell motility. Furthermore, the invasiveness of FGFRL1-deficient cells was lesser than that of wild-type KYSE520 cells. In the FGFRL1-deficient KYSE520 cells, actin filaments around the nucleus were observed sparsely, whereas the filaments along the plasma membranes were observed as frequently as those in the parent KYSE520 cells. These results demonstrate that FGFRL1 may be involved in regulation of protein expression, actin filament assembly and tumorigenic potential of ESCC cells.